Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet.
Environmental health perspectives
Adipose Tissue; Animals; Body Weight; Diet; Dietary Fats; Liver; Mice; Mice, Inbred C57BL; MicroRNAs; Models, Animal; Obesity; Polymerase Chain Reaction; RNA, Messenger; Receptors, Aryl Hydrocarbon; Signal Transduction
BACKGROUND: Obesity is a growing worldwide problem with genetic and environmental causes, and it is an underlying basis for many diseases. Studies have shown that the toxicant-activated aryl hydrocarbon receptor (AHR) may disrupt fat metabolism and contribute to obesity. The AHR is a nuclear receptor/transcription factor that is best known for responding to environmental toxicant exposures to induce a battery of xenobiotic-metabolizing genes.
OBJECTIVES: The intent of the work reported here was to test more directly the role of the AHR in obesity and fat metabolism in lieu of exogenous toxicants.
METHODS: We used two congenic mouse models that differ at the Ahr gene and encode AHRs with a 10-fold difference in signaling activity. The two mouse strains were fed either a low-fat (regular) diet or a high-fat (Western) diet.
RESULTS: The Western diet differentially affected body size, body fat:body mass ratios, liver size and liver metabolism, and liver mRNA and miRNA profiles. The regular diet had no significant differential effects.
CONCLUSIONS: The results suggest that the AHR plays a large and broad role in obesity and associated complications, and importantly, may provide a simple and effective therapeutic strategy to combat obesity, heart disease, and other obesity-associated illnesses.
Kerley-Hamilton, J., Trask, H., Ridley, C., Dufour, E., Ringelberg, C., Nurinova, N., Wong, D., Moodie, K., Shipman, S., Moore, J., Korc, M., Shworak, N. W., & Tomlinson, C. (2012). Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet.. Environmental health perspectives, 120 (9). http://dx.doi.org/10.1289/ehp.1205003
This is an open access PubMed Central article.